Handbook of Schizophrenia Spectrum Disorders, Volume I (eBook)

Foreword 5
Schizophrenia Spectrum Disorders: Insights from Views Across 100 years 5
Contents 9
Contributors 12
1 The Schizophrenia Construct After 100 Years of Challenges 17
The Schizophrenia Construct 19
A Unitary Concept 19
Categorical Models 19
Dimensional Models 22
Genetic Epidemiology 25
Familiality of Schizophrenia 29
Candidate Genes 30
Endophenotype Model Challenges 34
Current Challenges 39
Conclusions and Future Directions 42
References 43
2 Diagnosis and Classification of the Schizophrenia Spectrum Disorders 61
Introduction 62
Historical Aspects of Classification 63
Nosological Overview of the Schizophrenia Spectrum Disorders 65
Schizophrenia 65
Brief Psychotic Disorders 66
Schizoaffective Disorder 66
Personality Disorders 67
Schizotypal 68
Schizoid 68
Paranoid 68
Other Disorders 69
Bipolar Disorder with Psychotic Features 69
Major Depressive Disorder with Psychotic Features 70
Delusional Disorder 70
Obsessive Compulsive Disorder 70
Pervasive Developmental Disorders 70
Psychosis-Risk Syndromes 71
Critiques of Current Nosology 72
Differences Across Psychiatric Manuals 72
Validity of Existing Diagnostic Constructs 73
Reliability 74
Distinction of Disorders Within the Psychotic Spectrum 75
Organization of the Meta-Structure of Psychotic Disorders 75
Refining Schizophrenia Subtypes 77
Dimensional Representations 78
Use of More Proximal Indicators of Disorders 79
Etiology Related Classification 80
Cognition in Psychotic Disorders 81
Characterizing the Risk Syndrome for Psychosis 82
Culture and Ethnicity 83
Future Directions 84
Schizophrenia 84
Schizoaffective Disorder 85
Attenuated Psychotic Symptoms Syndrome 85
Personality Disorders 86
References 86
3 Toward a Multidimensional Continuum Model of Functional Psychoses for Research Purposes 100
Statement of Conundrum 101
Proof-of-Concept for a Multidimensional Continuum Model 103
Symptom Dimensions 108
Toward a Unitary Pathogenetic Mechanism 116
Conclusions and Future Directions 120
References 121
4 Irving Gottesman and the Schizophrenia Spectrum 129
Early Career 130
Heritability of Personality 130
The Maudsley Twin Study on Schizophrenia 131
The Schizoidia Concept 132
In Denmark 1972–1973: The Twin Study on Criminality 133
The Danish Dual Mating Study 133
The Professorships and the Books 134
The Discordant Twins' Offspring Study 134
The New Dual Mating Study 135
Endophenotypes 136
Recognition 137
References 137
5 Schizotypy: Reflections on the Bridge to Schizophrenia and Obstacles on the Road Ahead to Etiology and Pathogenesis 140
Reactions 143
Schizotypic Pathology/Schizophrenia Connection: Considering the ''Damn Strange Coincidence'' Argument 143
Leverage Gained with the Schizotypy Model 144
Reflections 145
Neuroimaging and Schizotypy/Schizophrenia: Selling Bridges v. Building Them. Where Are We, Are You Sure? 145
Major Impediments to Our Future Progress in Our Understanding Schizotypy and Schizophrenia 149
The Problem of Heterogeneity 149
The Problem of Rating in Schizotypy and Schizophrenia Research 151
Conclusions and Future Directions 152
References 152
6 Autistic Spectrum Disorders and Schizophrenia 155
Introduction 157
Autistic Spectrum Disorders: Diagnosis and Sub-types and Phenomenology 157
Epidemiology 158
Etiology 159
Genetics 160
Endophenotypes 161
Neuropathology and Brain Imaging 161
Infection and Immune Dysfunction 162
Early Recognition 163
Interventions 164
Psychosocial and Educational Interventions 164
Pharmacological Interventions 165
Autism and Schizophrenia: Co-morbid Association and Phenotypic Variations 167
Conclusions and Future Directions 168
References 169
7 One Hundred Years of Insanity: Genomic, Psychological, and Evolutionary Models of Autism in Relation to Schizophrenia 175
Introduction 176
"Autism" from Bleuler to the DSM 177
Phenotypic Structure of Autism and Schizophrenia Spectrum 180
Alternative Models for the Relationship of Schizophrenia with Autism 185
Conclusions and Future Directions 191
References 191
8 Quantifying the Dynamics of Central Systemic Degeneration in Schizophrenia 198
Background and Significance 199
Schizophrenia – A Complex Unsolved Problem 199
A Diseased Complex System? 201
Schizophrenia as a Degenerative Systemic Dysregulation 202
Theoretical Remarks 204
Quantifying Schizophrenia from Physiological Time Series 209
Nonlinear Analysis Methods and Physiological Data 209
Our Existing Nonlinear Analysis Results 211
Work in Progress 216
Conclusions: The Future of This Approach 217
Appendix 1: Simplified Schema of the Brain Circuitry Implicated in Schizophrenia Dysregulation 219
Appendix 2: Neural Complexity Layers that May Exhibit Suboptimal Dynamics in Schizophrenia 220
Appendix 3: Subject Recruitment and Data Collection 220
References 221
9 Schizophrenia Has a High Heritability, but Where Are the Genes? 229
Introduction 230
Likely Causes for Failure of Traditional Linkage/Candidate Gene Studies 233
The Genome-Wide Association Approach 234
Copy Number Variation in Schizophrenia 235
Common Disease, Common Variant or Rare Variant 236
The Dilemma of the Heterogeneous Sample 237
Reducing Genetic Heterogeneity Through Endophenotypes 237
Shared Genetic Susceptibility with Autism and Bipolar Disorder 238
Schizophrenia Research: Novel Approaches 239
Micro RNAs 240
Cytosine Methylation 240
Conclusion and Future Directions 242
References 243
10 Changes in Gene Expression in Subjects with Schizophrenia Associated with Disease Progression 247
Studies on the Human CNS Transcriptome: The First Indication of Progressive Changes in Gene Expression in Schizophrenia 248
Studies on the Human CNS Transcriptome: Outcomes from the Use of Microarrays 249
Studies on the Human CNS Transcriptome: Outcomes from Pooling Microarray Sets 253
Studies on the Human CNS Transcriptome: Moving Beyond Microarray Studies 254
Conclusions and Future Directions 255
References 257
11 Amino Acids in Schizophrenia – Glycine, Serine and Arginine 262
Introduction 263
Glycine 264
D-Serine 265
Arginine 266
Conclusions and Future Directions 267
References 268
12 Developmental Consequences of Prenatal Exposure to Maternal Immune Activation 272
Introduction 273
Epidemiologic Overview 274
Modeling Maternal Immune Activation 274
Live Pathogens 275
Pathogen-Free Inflammatory Agents 276
Pro-inflammatory Cytokines 277
Summary of Preclinical Models 277
Behavioral Consequences of Prenatal Immune Activation 277
Relevance to Positive Symptoms 278
Relevance to Cognitive Symptoms 279
Summary of Behavioral Consequences 282
Neurochemical Consequences of Prenatal Immune Activation 283
Dopamine 283
Glutamate 284
GABA 286
Overall Impact on Neurotransmitter Systems 287
Conclusions & Future Directions
References 289
13 Glutamatergic Neurotransmission Abnormalities and Schizophrenia 295
Introduction 296
Glutamatergic Neurotransmission 297
Glutamate Neurotransmission and Schizophrenia 298
NMDAR Antagonist Administration 299
Imaging Studies and Glutamate Hypothesis of Schizophrenia 300
Postmortem Brain Studies of NMD/AMPA/Kainate Receptors in Schizophrenia 301
Neurodevelopmental Model of Schizophrenia and NMDAR Hypofunction 304
Conclusions and Future Studies 306
References 306
14 Mathematical Models in Schizophrenia 313
Introduction 314
Mathematical Models with Implications in Schizophrenia 315
Conceptual Models 316
Correlative Models 316
Deterministic Models 318
Stochastic Models 319
Artificial Neural Networks 320
Mechanistically Based Models 322
Conclusions and Future Directions 323
References 329
15 Methamphetamine-Associated Psychosis: A Model for Biomarker Discovery in Schizophrenia 334
Introduction 335
Epidemiology of Methamphetamine 335
Acute and Chronic Effects of Methamphetamine 336
MAP Clinical Features 336
MAP Clinical Course 336
MAP Diagnosis 338
Biomarker Discovery 339
Genetic Biomarkers for MAP Susceptibility 339
Genetic Biomarkers of MAP Clinical Course 340
Conclusions and Future Directions 342
References 344
16 What Does Proteomics Tell Us About Schizophrenia? 351
Schizophrenia 352
Proteomics 352
Methods for Differential Proteome Studies 353
Two-dimensional Gel Electrophoresis 353
Shotgun Proteomics 354
Validation Experiments 354
Metabolomics 354
Proteomics of Schizophrenia Brain Tissue 355
Cytoskeleton-Related Proteins 355
Calcium Buffering 357
Oligodendrocyte Dysfunction 357
Energy Metabolism 360
Conclusions and Future Directions 365
References 367
17 The Role of 3a-Hydroxy-5a-Pregnan-20-One in Mediating the Development and/or Expression of Schizophrenia Spectrum Disorders: Findings in Rodents Models and Clinical Populations 373
Introduction 375
Biosynthesis and Metabolism of 3a,5a-THP 377
Genes Implicated in 3a,5a-THP Dysregulation 377
Mechanisms of Action of 3a,5a-THP 377
Animal Models of Schizo-Affective Disorders and Alterations in 3a,5a-THP 378
Stress-Responding and 3a,5a-THP 378
Schizo-Affective Disorders and Stress-Responding 379
Prenatal Stress and 3a,5a-THP 379
Effects of Prenatal Stress on Offspring Before Puberty 380
Sex Differences in 3a,5a-THP and Incidence and Symptom Manifestation of Schizophrenia 383
Interactions of Therapeutics and Neurosteroids in Schizophrenia 383
Anti-psychotics, Anti-depressants and 3a,5a-THP 385
3a,5a-THP Actions in the PFC, Hippocampus, and/or VTA to Mediate Behaviors 388
3a,5a-THP's Biosynthesis and Social Approach 388
P, 3a,5a-THP and Social Approach/Avoidance Behaviors 389
P, 3a,5a-THP and Socially-Relevant Cognitive Performance 391
Social Isolation and 3a,5a-THP 392
Maternal Separation Stress and 3a,5a-THP 392
Hippocampal Lesions and Schizo-Affective Behaviors 393
Dopamine in Schizo-Affective Disorders 396
Dopamine Transporter Knock-Out Mouse Model 396
Cocaine, Schizo-Affective Disorders and 3a,5a-THP 397
Methamphetamine, Endoplasmic Reticulum, and Schizo-Affective Disorders 399
Other Genetic Mutations in Schizo-Affective Disorders 400
Conclusions and Future Directions 400
References 401
18 Neural Substrates of Emotion Dysfunctions in Patients with Schizophrenia Spectrum Disorders 411
Introduction 412
Emotion Induction 414
Visual Emotion Induction 414
Olfactory Emotion Induction 416
Emotion Recognition 419
Recognizing Emotional Facial Expressions 419
Interpreting Emotional Prosody 424
Interaction of Emotion and Cognition 425
Emotional Self-Concept 428
Conclusions and Future Directions 430
References 431
19 Brain Morphological Abnormalities at the Onset of Schizophrenia and Other Psychotic Disorders: A Review of the Evidence 436
Introduction 437
Schizophrenia 437
Bipolar Disorder 439
Schizophrenia Compared with Affective Psychoses 439
Schizophrenia Compared with Schizophrenia Spectrum Disorders 440
Trajectories of Brain Abnormalities and Specificity of Brain Morphologic Changes in Schizophrenia and BD 441
Conclusions and Future Directions 443
References 444
20 Mapping Prodromal Psychosis 449
Introduction 450
Definition of the High Risk for Psychosis 451
Structural Neuroimaging 452
Structural MRI in Established Psychosis 452
Grey Matter Volume Abnormalities in Prodromal Psychosis: Cross Sectional Studies 452
Grey Matter Changes During the Transition to Psychosis: Longitudinal Studies 454
Functional Neuroimaging 457
fMRI in Established Psychosis 457
Neurofunctional Correlates of an Enhanced Risk to Psychosis 457
Neurofunctional Mapping of Psychosis Transition 459
Neurophysiological Correlates of Antipsychotic Treatments in Early Psychosis 460
Brain Connectivity in the Pre-psychotic Phases 461
fMRI and Longitudinal Outcomes in Subjects at High Risk for Psychosis 461
Neurochemical Imaging 463
Dopamine 463
Dopamine and Psychosis 463
Dopamine Dysregulation Prior to the Onset of Psychosis 463
The Revised Dopamine Hypothesis of Schizophrenia 465
Glutamate 466
Glutamate in Established Psychosis 466
Glutamate Dysfunction in Prodromal Psychosis 466
Integration of Neuroimaging Findings Across Modalities 467
Conclusions 470
References 470
Afterword 476
The Future of the Schizophrenia Construct and Acquisition of New Knowledge 476
References 479
Contents to Volume II 480
Contents to Volume III 482
Contributors to Volume II 484
Contributors to Volume III 489
Index 493